Metabolic activity in and metabolic support of malperfused brain tissue.

The human brain consumes 20% of total oxygen (O2) while representing only 2% of the body mass. The main source of energy in human tissues including the brain is adenosine triphosphate (ATP). ATP enables all cellular process in the brain, such as protein synthesis, maintaining resting membrane potential or neurotransmitter cycling. Under physiological conditions, the rate of energy consumption is exactly balanced by the rate of ATP synthesis, which also correlates with the brain activity levels. Nevertheless, there is no ATP reservoir in the brain. That means that even short O2 deprivation have immediate and delayed detrimental effects on brain function.
ATP metabolism produces adenosine, inosine and hypoxanthine, which are lost from the brain into circulation under conditions of cerebral malperfusion. Once lost, ATP production via the Purine Salvage Pathway (PSP), a biological pathway in which ATP levels are restored, is hindered.
There is an age-related, steady increase in systolic blood pressure (BP) which is now considered part of the "normal" ageing process. The BP increase causes small artery remodelling, characterised by a decrease of vessel diameter, and increased wall thickness. Affected vessels, predominantly those situated in deep cortical grey matter and subcortical white matter areas and lacking substantial collaterals, become less capacious. As a result, cerebral blood flow (CBF) to downstream areas declines and a metabolic mismatch arises.
This project aims to investigate the consequences of reduced CBF and disturbed PSP on the ageing brain. We will further investigate ways of PSP support as a potential measure to counter age- and CBF-related brain changes to support healthy brain function in the aging human population.